Genetic Variant ENST00000369564.6:c.-289G>A (chr1-113905154-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000369564.6(AP4B1):c.-289G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AP4B1
ENST00000369564.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09

Publications

9 publications found

Variant links:

Genes affected

AP4B1 (HGNC:572): (adaptor related protein complex 4 subunit beta 1) This gene encodes a subunit of a heterotetrameric adapter-like complex 4 that is involved in targeting proteins from the trans-Golgi network to the endosomal-lysosomal system. Mutations in this gene are associated with cerebral palsy spastic quadriplegic type 5 (CPSQ5) disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

AP4B1 links:

DCLRE1B (HGNC:17641): (DNA cross-link repair 1B) DNA interstrand cross-links prevent strand separation, thereby physically blocking transcription, replication, and segregation of DNA. DCLRE1B is one of several evolutionarily conserved genes involved in repair of interstrand cross-links (Dronkert et al., 2000 [PubMed 10848582]).[supplied by OMIM, Mar 2008]

DCLRE1B Gene-Disease associations (from GenCC):

dyskeratosis congenita, autosomal recessive 8
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

DCLRE1B links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369564.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DCLRE1B	NM_001319947.2		c.-330-315C>T	intron	N/A	NP_001306876.1
DCLRE1B	NM_022836.4	MANE Select	c.-433C>T	upstream_gene	N/A	NP_073747.1	Q9H816
AP4B1	NM_001438373.1		c.-310G>A	upstream_gene	N/A	NP_001425302.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AP4B1	ENST00000369564.6	TSL:5	c.-289G>A	5_prime_UTR	Exon 1 of 10	ENSP00000358577.2	B1ALD1
AP4B1	ENST00000863120.1		c.-289G>A	5_prime_UTR	Exon 1 of 9	ENSP00000533179.1
AP4B1	ENST00000935537.1		c.-289G>A	5_prime_UTR	Exon 1 of 9	ENSP00000605596.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

181822

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

97384

African (AFR)

AF:

0.00

AC:

AN:

5508

American (AMR)

AF:

0.00

AC:

AN:

6774

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4734

East Asian (EAS)

AF:

0.00

AC:

AN:

7452

South Asian (SAS)

AF:

0.00

AC:

AN:

31570

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9090

Middle Eastern (MID)

AF:

0.00

AC:

AN:

690

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

106548

Other (OTH)

AF:

0.00

AC:

AN:

9456

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

2234

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

1.1

PromoterAI

0.056

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over